Antagonistic pathogen-mediated selection favours the maintenance of innate immune gene polymorphism in a widespread wild ungulate

Abstract

Toll-like Receptors (TLR) play a central role in recognition and host frontline defence against a wide range of pathogens. A number of recent studies have shown that TLR genes (Tlrs) often exhibit a large polymorphism in natural populations. Yet, there is little knowledge on how this polymorphism is maintained and how it influences disease susceptibility in the wild. In a previous work, we showed that some Tlrs exhibit similarly high levels of genetic diversity than Mhc and contemporary signatures of balancing selection in roe deer (Capreolus capreolus), an abundant and widespread ungulate in Europe. Here, we tested whether Mhc-Drb or Tlr (Tlr2, Tlr4 and Tlr5) diversity is driven by pathogen-mediated selection. We examined the relationships between their genotype (heterozygosity status and presence of specific alleles) and infections with Toxoplasma and Chlamydia, two intracellular pathogens known to cause reproductive failure in ungulates. We showed that Toxoplasma and Chlamydia exposures vary significantly across year and landscape structure with few co-infection events detected, and that the two pathogens act antagonistically on Tlr2 polymorphism. By contrast, we found no evidence of association with Mhc-Drb and a limited support for Tlr heterozygosity advantage. Our study confirmed the importance of looking beyond Mhc genes in wildlife immunogenetic studies. It also emphasized the necessity to consider multiple pathogen challenges and their spatiotemporal variation to improve our understanding of vertebrate defence evolution against pathogens.